The major focus of this project is to evaluate and treat patients with malignant brain tumors. Treatment protocols are designed with the specific input of laboratory-based researchers. This clinical-laboratory interaction allows the rapid introduction of novel treatment strategies with the intended long-range goal of improved survival and quality of life for patients with primary malignant tumors of the central nervous system. Modalities of therapy will include surgery, gamma knife radiosurgery, interstitial brachytherapy, radiation therapy, radiosensitizers, chemotherapy, and gene therapy alone or in combination. The approach is multidisciplinary and includes the expertise of neurosurgeons, neuro- oncologists, neurologists, radiotherapists, medical oncologists, neuropathologists, clinical research nurses, and laboratory-based scientists. Protocols are jointly developed with clinical and laboratory researchers and the data captured and analyzed with the support of biostatiticians and data managers. For this renewal period, we will emphasize the use of radiation in the treatment of these patients. Protocols in progress or under development include randomized trials with interstitial brachytherapy and hyperthermia, the use of experimental radiosensitizers such as the halogenated pyrimidines and the polyamine inhibitors, treatment using altered fractionation schemes such as hyperfractionated radiotherapy and accelerated hyperfractionation, and radiosurgery using the gamma-knife. Adjuvant chemotherapy and phase II drug studies, including gene therapy, for recurrent tumors will also remain as an integral component of our total approach to the patient. Correlative data support for laboratory studies that are a part of this grant will come from clinical trials. Tumor and normal tissue stored in the tissue bank will serve as the source of material for other projects in this grant that will evaluate the radiosensitivity and molecular basis for radiation response. The clinical laboratory correlations that develop will serve as the substrate for newer, more individualized specific treatment recommendations for patients that will hopefully control disease with minimal or no toxicity.